LAM Test: A New Cognitive Marker for Early Detection in Preclinical Alzheimer’s Disease

Article type: Research Article

Authors: García-Martínez, María^{a; b; *} | Pozueta-Cantudo, Ana^{a; b} | Lage, Carmen^{a; b; d} | Martínez-Dubarbie, Francisco^{a; b} | López-García, Sara^{a; b} | Fernández-Matarrubia, Marta^{a; b} | Corrales-Pardo, Andrea^{a; b; j} | Bravo, María^{a; b} | Cavada, Nadia C.^{a; b} | Anuarbe, Pedroⁱ | Infante, Jon^{a; b; e; f} | López-Higuera, José Miguel^{b; h; i} | Rodríguez-Cobo, Luis^h | Rodríguez-Rodríguez, Eloy^{a; b; e; f} | Butler, Christopher R.^{c; 1} | Sánchez-Juan, Pascual^{e; g; 1}

Affiliations: [a] Neurology Service, Marqués de Valdecilla University Hospital, Santander, Cantabria, Spain | [b] Institute for Research Marqués de Valdecilla (IDIVAL), Santander, Cantabria, Spain | [c] Department of Brain Sciences, Imperial College London, London, UK | [d] Atlantic Fellow for Equity in Brain health, Global Brain Health Institute, UCSF-TCD, San Francisco, CA, USA | [e] CIBERNED, Network Center for Biomedical Research in Neurodegenerative Diseases, National Institute of Health Carlos III, Madrid, Spain | [f] Deparment of Medicine and Psychiatry, University of Cantabria, Santander, Spain | [g] CIEN Foundation/Queen Sofia Foundation Alzheimer Center, Madrid, Spain | [h] CIBER-BBN, Instituto de Salud Carlos III, Madrid, Spain | [i] Photonics Engineering Group, Universidad de Cantabria, Santander, Spain | [j] Universidad Europea del Atlántico, Santander, Spain

Correspondence: [*] Correspondence to: María García Martínez, Avda. de Valdecilla 25, 39008, Santander, Cantabria, Spain. Tel.: +34605124384; E-mail: magarcia.mart@gmail.com.

Note: [1] These authors contributed equally to this work.

Abstract: Background:With the arrival of disease-modifying treatments, it is mandatory to find new cognitive markers that are sensitive to Alzheimer’s disease (AD) pathology in preclinical stages. Objective:To determine the utility of a newly developed Learning and Associative Memory face test: LAM test. This study examined the relationship between AD cerebrospinal fluid (CSF) biomarkers and performance on LAM test, and assessed its potential clinical applicability to detect subtle changes in cognitively healthy subjects at risk for AD. Methods:We studied eighty cognitively healthy volunteers from the Valdecilla cohort. 61% were women and the mean age was 67.34 years (±6.416). All participants underwent a lumbar puncture for determination of CSF biomarkers and an extensive neuropsychological assessment, including performance on learning and associative memory indices of the LAM-test after 30 min and after 1 week, and two classic word lists to assess verbal episodic memory: the Rey Auditory Verbal Learning Test (RAVLT) and the Free and Cued Selective Reminding Test (FCSRT). We analyzed cognitive performance according to amyloid status (A+ versus A–) and to ATN model (A–T–N–; A+T–N–; A+T+N–/A+T+N+). Results:Performance on the LAM-test was significantly correlated with CSF Aβ ratio. A+ participants performed worse on both learning (mean difference = 2.19, p = 0.002) and memory LAM measures than A– (mean difference = 2.19, p = 0.004). A decline in performance was observed along the Alzheimer’s continuum, with significant differences between ATN groups. Conclusions:Our findings suggest that LAM test could be a useful tool for the early detection of subjects within the AD continuum, outperforming classical memory tests.

Keywords: Alzheimer’s disease, associative memory, cognitive markers, early detection, long-term forgetting, neuropsychological assessment, preclinical Alzheimer’s disease

DOI: 10.3233/JAD-240067

Journal: Journal of Alzheimer's Disease, vol. 100, no. 3, pp. 1039-1053, 2024